Funds are requested to purchase a Zeiss LSM 510 laser-scanning confocal microscope for integration into the Genetics Training Program (GTP) Imaging Facility. The University of Wisconsin GTP encompasses more than 75 faculty trainers in 10 departments and 3 colleges. It is recognized as one of the premier programs worldwide for research and training in Genetics. To maintain and advance our leadership in this field and to continue to train the most promising scientists, it is essential to have access to the state-of-the-art instruments and facilities on which our research depends. A confocal microscope has become one of the most essential research tools in modern biology, regardless of the particular experimental organism or particular problem under investigation. However, we currently lack consistent, affordable access to a confocal microscope. To fill this need, we are applying here for funds to purchase a confocal microscope. Eight primary users who will manage and subsidize maintenance of the microscope are submitting this application on behalf of the entire GTP. With reliable access to a confocal microscope, GTP scientists will be able to (i) simultaneously observe the cellular and sub-cellular localization of three different molecules (ii) follow the in vivo expression and localization dynamics of multiple proteins; (iii) visualize thin optical sections of thick biological specimens; and (iv) obtain high-resolution 3-D reconstructions of their specimens. The addition of a confocal microscope to our imaging facility will have a major impact on the research programs of each of the primary users. These programs range from studies of yeast to mice, and address fundamental questions in biology from the regulation of gene expression to the molecular mechanisms of cell division, from embryonic and organ development to neural signaling and memory formation. Relevance: The ongoing studies of the primary users are yielding important insights into the biological processes underlying human disorders including cancer, birth defects, mental retardation, deafness, blindness, and neurodegeneration, among others. We also will attract new users from within the GTP, so an accessible confocal will broaden and strengthen the research programs of laboratories beyond those of the initial primary users. All of the GTP faculty are engaged in research of significant relevance to human health; most have current funding through NIH. ? ? ?